This invention relates to an improved process for preparing an alkyl-2-alkoxyimino-3-oxo-4-chlorobutyrate, an intermediate in the preparation of compounds having antibacterial activity. Specifically, alkyl-2-alkoxyimino-3-oxo-4-chlorobutyrates are obtained in good yield by chlorinating alkyl-2-alkoxy-3-oxobutyrates with sulfuryl chloride in the presence of a catalytic amount of a N,N-dialkyl-substituted carboxamide.
The compounds according to the present process are useful in preparing compounds of the formula ##STR1## The substituents represented by R.sup.5, R.sup.6, R.sup.7 and R.sup.8 are not defined herein since they are not within the scope of my invention but are defined in various U.S. patents some of which are cited hereinbelow. The substituent R.sup.4 is a part of the subject matter of my invention and will be defined hereinafter in the detailed description of my invention. Specific compounds of the above formula and the method of making same are disclosed in U.S. Pat. Nos. 4,203,899, 4,278,671 and 4,294,960. These compounds are known to have antibacterial activity against a broad spectrum of bacteria in both humans and animals.
A known method for preparing alkyl-2-alkoxyimino-3-oxo-4-chlorobutyrates using sulfuryl chloride is disclosed in the '960 patent cited hereinabove. By this process sulfuryl chloride is reacted with the appropriate oxobutyrate in acetic acid to obtain the desired chlorinated compound. This process is hampered by the need to use a complicated multistep extraction and purification procedure to isolate the final product. On a commercial scale the disadvantages of such a procedure become readily apparent, i.e., increased costs due to longer production time and use of greater amounts of reagents, additional waste streams and attendant problems in handling and disposing of the waste streams.
I have found that the chlorination of alkyl-2-alkoxyimino-3-oxobutyrates using sulfuryl chloride is improved substantially when the reaction is conducted in the presence of a catalytic amount of a N,N-dialkyl-substituted carboxamide. In particular, significantly better yields of alkyl-2-alkoxyimino-3-oxo-4-chlorobutyrates are produced through the use of catalytic amounts of a N,N-dialkyl-substituted carboxamide than when no N,N-dialkyl-substituted carboxamide is used. Moreover, the crude product may be used in unpurified form without interfering reactions from by-product contaminants, such as the dichlorinated compound alkyl-2-alkoxy-3-oxo-4,4-dichlorobutyrate.